Washington, DC -- December 10, 2013 --An implant (RNS System, NeuroPace) designed to detect abnormal preseizure electrical activity in the brain and respond by delivering imperceptible levels of electrical stimulation to normalise brain activity before an individual experiences seizures is safe and effective, as previously reported in a pivotal trial patients with epilepsy with partial-onset seizures refractory to treatment, according to a long-term evaluation presented here at the 67th Annual Meeting of the American Epilepsy Society (AES).

The seizure reduction in patients treated with the [implant] improved over the first 2 years and now has been sustained in the following years. Treatment remained safe over time, said Gregory Bergey, MD, Johns Hopkins Medical Institute, The Johns Hopkins University, Baltimore, Maryland, on December 9. The results continue to support the safety and effectiveness that was established in the pivotal study.

In the long-term study, 256 adults (mean age 34 years; 125 women) with medically intractable partial-onset seizures (mesial temporal lobe: n = 111, 43%) localised to 1 or 2 (n = 124, 48%) seizure foci in the brain were enrolled beginning in 2006 (enrollment is continuing) and were followed for a battery of criteria. Of the total patients evaluated, 191 were from the pivotal study and an additional 65 subsequently received implants in the feasibility study. Assessments included the percentage change in the frequency of seizures, percentage of patients with ?50% reduction in seizures, and safety as determined by adverse events including depression, impaired memory, and anxiety.

The patients were veterans of epilepsy, with a mean epilepsy duration of 19.6 years and a 28-day mean seizure frequency of 50.7 (median 10.2/28 days). Most were taking antiepileptic drugs (AEDs; mean 2.9 AEDs). Prior intracranial monitoring, epilepsy surgery, and vagus nerve stimulation had been done in 166 (65%), 86 (34%), and 82 (32%) of the patients, respectively. The median follow-up to date has been 4.5 years with 1,200 patient-implant-years.

The median percentage reduction at 1 year was 38.9% and at 2 years was 51.1%. Twenty percent of the patients had freedom from seizures for ?6 months. In a subanalysis, the progressive improvement over time was statistically similar in 99 patients whose postimplant medication was changed versus 98 patients whose medication regimen was unaltered after device implantation.

The overall rate of device-related AEs declined with time, especially after the first year. AEs related to the device included implant-site infection (8.6%), need for device removal (4.7%), premature battery depletion (4.3%; a problem resulting from defective batteries that has been solved by use of a different supplier), device-lead damage (3.5%), and device-lead revision (7%).

The SAE event rate was 0.010/implant-year for haemorrhage and 0.023/implant-year for infection. Eleven patients died (4.3%): 2 suicides, 1 status epilepticus, 1 lymphoma, and 7 sudden unexpected deaths in epilepsy (SUDEP). Two of the SUDEP events occurred in sham subjects who did not receive stimulation. The SUDEP rate was 4.5/1,000 patient-stimulation-years.

Device treatments are emerging as options for treatment of medically refractory epilepsy. The risks with the RNS system [implant] are consistent with the anticipated risks of an implanted device and of seizures, concluded Dr. Bergey.

Clinical research will continue to explore stimulation targets and the effects of different stimulation parameters. The optimal stimulation parameters could not be established during the double-blind pivotal trial. These parameters may differ between different patients and stimulation sites. he added.

The RNS System received US Food and Drug Administration premarket approval in November 2013.